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Research ArticleClinical Studies

Impact of Renin–angiotensin System Inhibitors on the Efficacy of Anti-PD-1/PD-L1 Antibodies in NSCLC Patients

TAKEHIRO TOZUKA, NORIKO YANAGITANI, HIROSHI YOSHIDA, RYO MANABE, SHINSUKE OGUSU, RYOSUKE TSUGITOMI, HIROAKI SAKAMOTO, YOSHIAKI AMINO, RYO ARIYASU, KEN UCHIBORI, SATORU KITAZONO, MASAHIRO SEIKE, AKIHIKO GEMMA and MAKOTO NISHIO
Anticancer Research April 2021, 41 (4) 2093-2100; DOI: https://doi.org/10.21873/anticanres.14980
TAKEHIRO TOZUKA
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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NORIKO YANAGITANI
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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HIROSHI YOSHIDA
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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RYO MANABE
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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SHINSUKE OGUSU
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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RYOSUKE TSUGITOMI
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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HIROAKI SAKAMOTO
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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YOSHIAKI AMINO
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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RYO ARIYASU
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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KEN UCHIBORI
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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SATORU KITAZONO
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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MASAHIRO SEIKE
2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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AKIHIKO GEMMA
2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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MAKOTO NISHIO
1Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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  • For correspondence: mnishio@jfcr.or.jp
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Abstract

Background/Aim: The Renin–Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies. Patients and Methods: This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi. Results: A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11). Conclusion: The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.

Key Words:
  • Renin–angiotensin system inhibitors
  • non-small cell lung cancer
  • anti-programmed cell death 1/ligand-1 antibodies
  • immunotherapy
  • Received February 9, 2021.
  • Revision received February 18, 2021.
  • Accepted February 19, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (4)
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Impact of Renin–angiotensin System Inhibitors on the Efficacy of Anti-PD-1/PD-L1 Antibodies in NSCLC Patients
TAKEHIRO TOZUKA, NORIKO YANAGITANI, HIROSHI YOSHIDA, RYO MANABE, SHINSUKE OGUSU, RYOSUKE TSUGITOMI, HIROAKI SAKAMOTO, YOSHIAKI AMINO, RYO ARIYASU, KEN UCHIBORI, SATORU KITAZONO, MASAHIRO SEIKE, AKIHIKO GEMMA, MAKOTO NISHIO
Anticancer Research Apr 2021, 41 (4) 2093-2100; DOI: 10.21873/anticanres.14980

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Impact of Renin–angiotensin System Inhibitors on the Efficacy of Anti-PD-1/PD-L1 Antibodies in NSCLC Patients
TAKEHIRO TOZUKA, NORIKO YANAGITANI, HIROSHI YOSHIDA, RYO MANABE, SHINSUKE OGUSU, RYOSUKE TSUGITOMI, HIROAKI SAKAMOTO, YOSHIAKI AMINO, RYO ARIYASU, KEN UCHIBORI, SATORU KITAZONO, MASAHIRO SEIKE, AKIHIKO GEMMA, MAKOTO NISHIO
Anticancer Research Apr 2021, 41 (4) 2093-2100; DOI: 10.21873/anticanres.14980
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Keywords

  • Renin–angiotensin system inhibitors
  • Non-small cell lung cancer
  • anti-programmed cell death 1/ligand-1 antibodies
  • immunotherapy
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